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Gastroesophageal Reflux Disease
Anna Cecilia S. Tenorio, MD
Fozia Akhtar Ali, MD
image BASICS
DESCRIPTION
Backward flow of stomach acid or contents into the mouth or esophagus that occurs for twice a week for several weeks, causing symptoms of discomfort often described as heartburn, acid indigestion, and acid reflux
EPIDEMIOLOGY
Incidence
Incidence: 5 per 1,000 person-years
Prevalence
  • Prevalence of gastroesophageal reflux disease (GERD) is about 10-20% in the United States and United Kingdom, and in Asia is about 5%.
  • 40% of adults in the United States have symptoms of reflux.
  • 50-85% of GERD patients have nonerosive reflux disease
  • Chronic GERD is a risk factor for Barrett esophagus.
  • 10% of patients with chronic GERD have Barrett esophagus.
  • Risk of adenocarcinoma without Barrett esophagus and no dysplasia: 0.1-0.5% per patient year
  • Risk of adenocarcinoma with Barrett esophagus and high-grade dysplasia: 6-19% per patient-year
  • Pediatric population: Regurgitation occurs at least once a day in 67% of 4-month-old infants. Prevalence decreased to 21% at age 6 to 7 months, and down to 5% at age 10 to 12 months.
ETIOLOGY AND PATHOPHYSIOLOGY
  • The pattern and mechanism of reflux varies depends on the severity of disease.
  • GERD begins with contact of acidic stomach contents with the squamous mucosal lining of the esophagus, at the esophagogastric junction (EGJ).
  • Usually affected by inappropriate transient lower esophageal sphincter relaxation. Foods that are spicy, acidic and high in fat, caffeine, alcohol, tobacco, anticholinergic medications, nitrates, smooth muscle relaxants affect LES relaxation.
  • Most people with severe GERD have some evidence of hiatal hernia, which affects GERD by (1):
    • Trapping acid in the hernia sac
    • Impaired acid emptying
    • Increasing retrograde acid flow rate
    • Reducing the EGJ sphincter pressure
    • Increased frequency of transient lower esophageal sphincter relaxations
Genetics
Genetic heterogeneity has been associated with GERD.
RISK FACTORS
  • Obesity
  • Hiatal hernia
  • Scleroderma
  • Alcohol use
  • Tobacco use
  • Pregnancy
GENERAL PREVENTION
  • Decrease consumption of food and beverage triggers such as spicy, fatty foods, alcohol and caffeine
  • Weight loss
  • Avoid lying down soon after eating a meal.
  • Tobacco and alcohol cessation
  • Elevated head of bed when sleeping at night
  • Avoid having meals close to bedtime.
  • Infants: Use car seat for 2 to 3 hours after meals; thickened feedings
COMMONLY ASSOCIATED CONDITIONS
  • Nonerosive esophagitis
  • Erosive esophagitis
  • Irritable bowel syndrome
  • Peptic ulcer disease
  • Extraesophageal reflux: aspiration, chronic cough, laryngitis, vocal cord granuloma, sinusitis, otitis media
  • Halitosis
  • Hiatal hernia: acid pocket (zone of high acidity in the proximal stomach after a meal) above the diaphragm in patients with hiatal hernia is a risk factor (2)[B]
  • Peptic stricture: 10% of patients with GERD
  • Barrett esophagus
  • Esophageal adenocarcinoma
image DIAGNOSIS
  • Typical symptoms: acid regurgitation, heartburn, dysphagia (mostly post prandial)
  • Atypical symptoms: epigastric fullness/pressure/pain, dyspepsia, nausea, bloating, belching, chest pain, lump in throat
  • Extraesophageal signs and symptoms: chronic cough, bronchospasm, wheezing, hoarseness, sore throat, asthma, laryngitis, dental erosions
PHYSICAL EXAM
Typically unremarkable
  • BMI
  • Rare epigastric tenderness or palpable epigastric mass
  • Look for stigmata of chronic systemic disease or alcohol use.
DIFFERENTIAL DIAGNOSIS
  • Infectious esophagitis (Candida, herpes, HIV, cytomegalovirus)
  • Chemical esophagitis
  • Pill-induced esophagitis
  • Eosinophilic esophagitis
  • Nonulcer dyspepsia
  • Biliary tract disease
  • Radiation injury
  • Crohn disease
  • Angina/coronary artery disease
  • Esophageal stricture or anatomic defect (ring, sling)
  • Esophageal adenocarcinoma
  • Achalasia
  • Scleroderma
  • Peptic ulcer disease
DIAGNOSTIC TESTS & INTERPRETATION
Patients with typical symptoms of GERD and without alarm symptoms (dysphagia odynophagia, weight loss, early satiety, anemia, new onset, male >50 years) should be initially treated empirically with antisecretory agents without any further diagnostic testing.
Initial Tests (lab, imaging)
  • Indication for blood work depends on clinical presentation. Check for anemia (history of bleeding; or possible poor B12 absorption due to chronic proton pump inhibitor [PPI] use).
  • Patients with GERD presenting with noncardiac chest pain should undergo evaluation first before the onset of treatment.
Diagnostic Procedures/Other
  • Upper endoscopy
    • First-line diagnostic test for those with alarm signs and uncontrolled symptoms (2)[B]
    • Indications for UGI endoscopy
      • Alarm symptoms such as dysphagia, bleeding, anemia, weight loss, recurrent vomiting
      • Persistent typical GERD symptoms despite empiric treatment of twice-daily PPI for 4 to 8 weeks
      • Men >50 years old with chronic GERD (>5 years) and other risk factors: hiatal hernia, high BMI, tobacco use, high abdominal fat distribution
      • History of severed erosive esophagitis to assess healing and check for Barrett esophagus and other UGI pathology
      • Surveillance in patients with history of Barrett's esophagus
    • ˜50-70% of patients with heartburn have negative endoscopy findings
  • Savary-Miller classification
    • Grades esophagitis based on endoscopy
      • Grade I: ≥1 nonconfluent reddish spots, with or without exudate
      • Grade II: erosive and exudative lesions in the distal esophagus; may be confluent but not circumferential
      • Grade III: circumferential erosions in the distal esophagus
      • Grade IV: chronic complications such as deep ulcers, stenosis, or scarring with Barrett metaplasia
  • Esophageal manometry
    • Not recommended for primary GERD diagnosis; a second option for those with GERD and normal endoscopy (2)[B]
    • Diagnose motility disorders: functional heartburn, achalasia, and distal esophageal spasm.
    • Used to evaluate peristaltic function preoperatively and to record LES pressure
  • Ambulatory reflux (ph) monitoring
    • Used to evaluate possible excessive esophageal acid exposure to those with GERD, normal endoscopy and no PPI response (2)[B]
    • Used also to document frequency of reflux
    • Need to discontinue PPI use for 7 days prior to procedure
  • Barium swallow: not used for GERD diagnosis. Used to evaluate complaints of dysphagia to outline anatomic abnormalities (hiatal hernia)
Test Interpretation
  • Acute inflammation (especially eosinophils)
  • Epithelial basal zone hyperplasia seen in 85%
  • Barrett epithelial change: Gastric columnar epithelium replaces squamous epithelium in distal esophagus (metaplasia).
P.401

image TREATMENT
GENERAL MEASURES
Lifestyle changes are first-line intervention:
  • Elevate head of bed (2)[B].
  • Avoid meals 2 to 3 hours before bedtime (2)[B].
  • Avoid stooping, bending and tight-fitting garments.
  • Avoid medications that relax LES (anticholinergic drugs; calcium channel blockers).
  • Weight loss (2)[B]
  • Tobacco cessation and alcohol avoidance
  • Limit consumption of patient-specific food triggers (global elimination of all reflux-causing foods is not necessary or beneficial).
  • Stepped therapy
    • Phase I: lifestyle and diet modifications, antacids plus H2 blockers or PPIs
    • Phase II: If symptoms persist, consider endoscopic evaluation.
    • Phase III: If symptoms still persist, consider surgical options.
MEDICATION
First Line
  • H2 blockers in equipotent oral doses (e.g., cimetidine 800 mg BID or 400 mg QID, ranitidine 150 mg BID, famotidine 20 mg BID, or nizatidine 150 mg BID)
    • Renally dosed
  • PPIs: Irreversibly bind proton pump (H+/K+ ATPase), effective onset within 4 days. Omeprazole 20 to 40 mg/day, lansoprazole 15 to 30 mg/day, dexlansoprazole 30 mg/day, pantoprazole 40 mg/day, rabeprazole 20 mg/day, esomeprazole 40 mg/day
    • No major differences in efficacy among PPIs (3)[A]
    • Dose 30 to 60 minutes before meals with the exception of dexlansoprazole (2)[A].
    • PPIs may increase risk of hypomagnesemia, hip fracture, Clostridium difficile infection, vitamin B12 deficiency, and community acquired pneumonia.
  • PPI is more effective than H2 blocker and prokinetics for healing erosive esophagitis and nonerosive esophagitis (4)[A].
  • Erosive esophagitis: 8 weeks of PPI effective in 90%
Pediatric Considerations
Antacids or liquid H2 blockers and PPIs are available. Prokinetics have a minimal role due to safety concerns and limited efficacy.
Second Line
  • Antacids or barrier agents (sucralfate 1 g PO QID 1 hour before meals and at bedtime for 4 to 8 weeks) may relieve breakthrough symptoms.
  • Prokinetics: metoclopramide 5 to 10 mg before meals
  • Baclofen as add-on therapy with a PPI
  • Precautions
    • Blood dyscrasias and anemia with PPIs and H2 blockers
    • Metoclopramide is a dopamine blocker; risk of dystonia and tardive dyskinesia
    • Tachyphylaxis may occur with H2 blockers.
  • Significant possible interactions
    • PPIs and H2 blockers: multiple cytochrome P450 drug interactions; that is, warfarin, phenytoin, antifungals, digoxin
SURGERY/OTHER PROCEDURES
  • Laparoscopic fundoplication (wrapping gastric fundus around distal esophagus) increases pressure gradient between stomach and esophagus.
  • Bariatric surgery
    • Surgery indicated if: Patient desires to discontinue medical therapy, has side effects with medical therapy, large hiatal hernia, esophagitis refractory to medical therapy, or refractory symptoms (4)[A].
    • Pre-op ambulatory pH monitor is mandatory in patients without evidence of erosive esophagitis (4)[A].
    • Rule out esophageal dysmotility prior to surgery by manometry to rule out achalasia or scleroderma like esophagus (4)[A].
    • Best surgical response is seen in patients with typical symptoms who respond well to PPI therapy.
    • If it is estimated that a patient will require >10 years of PPI treatment, surgery may be more cost-effective.
    • Bariatric surgery can be considered for patients with comorbid obesity. Gastric bypass is preferred (4)[A].
Pediatric Considerations
Surgery for severe symptoms (apnea, choking, persistent vomiting)
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Monitor and follow symptoms over time.
  • Repeat endoscopy at 4 to 8 weeks if there is a poor symptomatic response to medical therapy, especially in older patients.
  • Endoscopic surveillance every 2 to 3 years in patients with Barrett esophagus to screen for malignant transformation (in patients who would opt for treatment if cancer is detected)
DIET
Avoid foods that can trigger or make symptoms worse.
PATIENT EDUCATION
Lifestyle and dietary modifications: Eat small meals; avoid lying down soon after meals; elevate head of bed; weight loss; smoking cessation; avoid alcohol and caffeine.
PROGNOSIS
  • Symptoms and esophageal inflammation often return promptly when treatment is withdrawn. To prevent relapse of symptoms, continue antisecretory therapy (in addition to lifestyle and dietary modifications).
    • PPI maintenance therapy likely improves quality of life better than H2 blocker maintenance.
    • Full-dose PPIs are more effective than half-dose for maintenance (4)[A].
    • In erosive esophagitis, daily maintenance therapy with PPI prevents relapse; intermittent PPI therapy not as effective (2)[A]
  • Medical and surgical therapy are equally effective for symptom reduction (4)[A].
  • Antireflux surgery
    • 90-94% symptom response. Patients with persistent symptoms should have repeat anatomic evaluation (endoscopy or esophagram).
    • Some surgically treated patients eventually require medical therapy.
  • Regression of Barrett epithelium does not routinely occur despite aggressive medical or surgical therapy.
REFERENCES
1. Lee YY, McColl KE. Pathophysiology of gastroesophageal reflux disease. Best Pract Res Clin Gastroenterol. 2013;27(3):339-351.
2. Kahrilas PJ, Shaheen NJ, Vaezi MF, et al. American Gastroenterological Association medical position statement on the management of gastroesophageal reflux disease. Gastroenterology. 2008;135(4):1383. e5-1391.e5.
3. Agency for Healthcare Research and Quality. Comparing effectiveness of management strategies for gastroesophageal reflux disease. An update to the 2005 report. http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?productid=781&pageaction=displayproduct/. Accessed 2015.
4. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(10):308-328.
Additional Reading
&NA;
  • Anderson WD III, Strayer SM, Mull SR. Common questions about the management of gastroesophageal reflux disease. Am Fam Physician. 2015;91(10):692-697.
  • Campanozzi A, Boccia G, Pensabene L, et al. Prevalence and natural history of gastroesophageal reflux: a pediatric prospective survey. Pediatrics. 2009;123(3):779-783.
  • El-Serag HB, Sweet S, Winchester CC, et al. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014;63(6):871-880.
See Also
&NA;
Algorithms: Abdominal Pain, Upper; Dyspepsia
Codes
&NA;
ICD10
  • K21.9 Gastroesophageal reflux disease without esophagitis
  • K21.0 Gastro-esophageal reflux disease with esophagitis
Clinical Pearls
&NA;
  • GERD is primarily diagnosed by history.
  • GERD should be considered in nonsmokers who have chronic cough (>3 weeks).
  • PPI treatment does not appear to inhibit neoplastic progression in Barrett esophagus.
  • No evidence to support that patients with GERD should routinely be tested for Helicobacter pylori.
  • Empiric treatment with H2 blockers or PPI leads to symptomatic relief in most cases. Persistent symptoms should be evaluated with endoscopy.